Viruses and plasmids have been shown to control the production of several important bacterial toxins. We will analyze the synthesis of heat-labile enterotoxin in Escherichia coli as a model for plasmid directed toxin production and diphtherial toxin in Corynebacterium diphtheriae as a model for control of toxinogenesis by bacteriophage. Our long range goals for the study of each of these two model systems are to characterize the structural and regulatory genes controlling toxinogenesis, to identify and characterize their gene products, to analyze the biochemical and molecular mechanisms controlling toxinogenesis, and to apply our findings toward improved control of infectious diseases in humans. Mutants of E. coli and C. diphtheriae that are altered in toxinogenesis will be used to analyze toxin structure and activity, toxin immunochemistry, regulation of toxin biosynthesis and secretion, role of toxin in normal bacterial physiology, importance of toxin for bacterial virulence, and development of improved immunization methods through the rational application of microbial genetics and biochemistry to the practical problems of vaccine development. This research will contribute at a basic level to an improved understanding of fundamental biological mechanisms involved in toxinogenesis and microbial pathogenesis, and at the applied level it may contribute to improved control of medically important human diseases and economically important veterinary diseases.